We are studying the structure and function of signal transduction proteins, specifically heterotrimeric GTP-binding proteins (G proteins) and G protein-coupled receptors (GPCRs). Our specific goals are to understand the structural basis of function by designing and evaluating mutant forms of the G proteins and receptors. One category of mutants contains two or more histidines placed so that they could be bridged by a metal ion. Such a link could cause metal-dependent activation or inactivation of the protein. In known structures, this would enhance our knowledge of the activation process; in unknown structures, this would also yield distance constraints. The CGL facilities are crucial for many steps of this research: viewing crystallographic or modelled structures to design mutants, rationalizing the properties of the mutants, and to develop hypotheses about protein-ligand and protein-protein interactions, and about conformational changes involved in activation and deactivation.